Inside-out integrin activation pathway

Chemokines bind to their GPCRs on leukocytes, triggering a series of intracellular signals, which lead to the activation of Rap1. Rap1 is crucial for integrin activation. In order to assure anchorage to the cytoskeleton and optimal integrin activation, talin and kindlin 3 must bind to the beta subunit of the integrin. Activated integrins have a fully extended, high-affinity structure, with an open ligand binding site.